The overall goal of this project is to describe the variation in the dynamics of olfactory adaptation and recovery, and to relate the contribution of per-receptor mechanisms involved in odorant transport and clearance to this variation. The proposed research will pursue this goal through experimental and clinical studies aimed at elucidating the range and sources of variation in adaptation, and by developing a mathematical model of olfactory adaptation to serve as a unifying framework. The three specific aims of the proposed research are: (1) to evaluate the extent to which peri-receptor processes involved in odorant transport and clearance can modulate the time-course of adaptation and recovery, (2) to characterize the variation in the dynamic response of a challenged olfactory system as a function and clinical etiology and age, especially among clinic patients who report rapid and prolonged adaptation to ambient and food-mediated odors, and (3) to develop a mathematical transport model of olfactory adaptation capable of simulating the odorant transport, accumulation and clearance in the nasal/olfactory region, and if appropriate, the time-course of receptor adaptation and recovery (as measured in Project 1). This project will increase our understanding of the role of peri-receptor events in the development of both short- and long-term adaptation and recovery. Moreover, through interactions with Project 4 in this CCRC we will obtain a better understanding of the relationship between receptor and peri-receptor events in adaptation. The project has important implications for efforts to remediate dynamic olfactory loss in real world situations. Although rapid adaptation is frequently reported in clinical evaluations, current clinical assessments of olfactory dysfunction do not include tests that measure rates of adaptation and recovery. However, abnormal rates of adaptation or recovery could significantly diminish olfactory sensitivity, as well as render individuals more vulnerable to hazards such as gas leaks, fires and spoiled food. Aberrant adaptation and/or recovery could also contribute to nutritional problems by reducing the perception and enjoyment of food. Peri-receptor mechanisms that contribute significantly to dynamic olfactory loss may be amenable to therapeutic interventions for restoring certain aspects of olfactory function.